Efficacy of Three ACTs for the Treatment of Falciparum Malaria in Maradi Niger

This study is currently recruiting participants.
Verified February 2014 by Epicentre
Sponsor:
Collaborator:
Centre de Recherche Médicale et Sanitaire (Cermes), Niamey
Information provided by (Responsible Party):
Epicentre
ClinicalTrials.gov Identifier:
NCT01755559
First received: December 19, 2012
Last updated: February 4, 2014
Last verified: February 2014
  Purpose

Study treatments:

  • Artemether-lumefantrine
  • Artesunate-amodiaquine
  • Dihydroartemisinin-piperaquine

Location:

Maradi, Niger

Principal Objective:

To measure the clinical and parasitological efficacy of the three artemisinin combination therapies over a period of 42 days from the start of treatment and with polymerase chain reaction assay (PCR) adjustment.

Secondary objectives:

  • To determine the blood concentration of the non-artemisinin component of the treatment (lumefantrine, desethylamodiaquine or piperaquine) at day 7
  • To assess the incidence of adverse events during the follow-up period;
  • To measure speed of parasite clearance

Methods:

In vivo non comparative study as for WHO standardised protocol. The study also measure the concentration of the non-artemisinin component.

Target population:

Children under 5 years of age consulting the integrated health centres of Andoumé and Dix-sept portes in Maradi.

Sample size:

221 patients per study treatment; 663 patients in total.

Treatment allocation:

Random.

Outcomes:

  • Early treatment failure,
  • Late clinical failure,
  • Late parasitological failure,
  • Adequate clinical and parasitological response.

Analysis:

  • Cumulative success or failure rate (Kaplan-Meier analysis).
  • Proportions of early treatment failures, late clinical failures, late parasitological failures, and adequate clinical and parasitological response (called also Per-protocol analysis).

Condition Intervention Phase
Malaria
Drug: Artesunate-amodiaquine
Drug: Dihydroartemisinin-piperaquine
Drug: Artemether-lumefantrine
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Efficacy of Artesunate-amodiaquine, Dihydroartemisinin-piperaquine and Artemether-lumefantrine Combination Therapies for the Treatment of Uncomplicated Plasmodium Falciparum Malaria in Children Aged 6 to 59 Months in Maradi, Niger 2012-13

Resource links provided by NLM:


Further study details as provided by Epicentre:

Primary Outcome Measures:
  • Adequate clinical and parasitological response [ Time Frame: 42 days after treatement start ] [ Designated as safety issue: No ]
    Absence of parasitaemia on day 42, irrespective of axillary temperature, in patients who did not previously meet any of the criteria of early treatment failure, late clinical failure or late parasitological failure.


Secondary Outcome Measures:
  • Early treatment failure [ Time Frame: 1 to 3 days after tratment start ] [ Designated as safety issue: No ]
    • General danger signs or signs of severe malaria on days 1, 2, or 3, in the presence of parasitaemia , or
    • Parasitaemia on day 2 higher than on day 0, irrespective of axillary temperature, or
    • Parasitaemia on day 3 with axillary temperature ≥ 37.5°C, or
    • Parasitaemia on day 3 ≥ 25% count on day 0 irrespective of axillary temperature.

  • Late clinical failure [ Time Frame: from day 4 to day 42 after treatment start ] [ Designated as safety issue: No ]
    • General danger signs or severe malaria in the presence of parasitaemia on any day between day 4 and day 42 in patients who did not previously meet any of the criteria of early treatment failure; or
    • Presence of parasitaemia on any day between day 4 and day 42 with axillary temperature ≥ 37.5 °C in patients who did not previously meet any of the criteria of early treatment failure.

  • Late Parasitological Failure [ Time Frame: from day 7 to day 42 after treatment start ] [ Designated as safety issue: No ]
    - Presence of parasitaemia on any day between day 7 and day 42 with axillary temperature < 37.5 °C in patients who did not previously meet any of the criteria of early treatment failure or late clinical failure.


Estimated Enrollment: 663
Study Start Date: June 2013
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Artesunate-amodiaquine
Efficacy estimates at 95%
Drug: Artesunate-amodiaquine
antimalarial ACT
Other Name: AS-AQ Winthrop® Sanofi Aventis
Dihydroartemisinin-piperaquine
Efficacy estimates at 95%
Drug: Dihydroartemisinin-piperaquine
antimalarial ACT
Other Name: Euratesim, Sigma-Tau
Artemether-lumefantrine
Efficacy estimates at 95%
Drug: Artemether-lumefantrine
antimalarial ACT
Other Name: Coartem, Novartis

  Eligibility

Ages Eligible for Study:   6 Months to 59 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age between 6 and 59 months
  • Weight ≥ 5 kg
  • Mono-infection with P. falciparum detected by microscopy
  • Parasitic density between 2,000 and 200,000 asexual forms /µL of blood
  • Axillary temperature ≥ 37.5°C or history of fever during the previous 24 hours
  • Ability and willingness to comply with the protocol for the duration of the study and to comply with the study visit schedule (home is within one hour of walk from the outpatient department, no near-term travel plans, etc.)
  • Consent of a parent or guardian who is at least 18 years of age.

Exclusion Criteria:

  • Presence of general danger signs as defined by the WHO,
  • Presence of signs of severe malaria according to the definitions of WHO,
  • Severe anemia (haemoglobin <5 g/dL),
  • Known history of symptomatic cardiac arrhythmias or with clinically relevant bradycardia,
  • Family history of sudden death or of congenital prolongation of corrected QT interval,
  • Use of antiarrhythmics or neuroleptics,
  • Known history of hypersensitivity to any of the study medications,
  • Severe malnutrition (defined as a weight-height ratio of < -3 z-score according to the 2006 WHO reference (20) and / or a mid-upper arm circumference lower than 115 mm and / or the presence of symmetrical oedema of the feet),
  • Presence of a febrile condition due to a disease other than malaria (i.e. measles, acute lower respiratory tract infection, otitis media, tonsillitis, abscess, severe diarrhoea with dehydration, etc.)
  • History of a full treatment course with one of the three study drugs in the past 28 days. The prior incomplete intake of one of the three study drugs or prior intake of antimalarial drugs not being tested in the study does not exclude a patient from participating in this study. However, information on these previous treatments will be carefully recorded.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01755559

Contacts
Contact: Francesco Grandesso, MSc +33 1 40 21 54 63 francesco.GRANDESSO@epicentre.msf.org
Contact: Jean-François Etard, PhD +33 1 40 21 54 82 jean-francois.etard@epicentre.msf.org

Locations
Niger
Andoumé Health Centre Recruiting
Maradi, Niger
Contact: Ousmane Guindo, MD    +227 99 44 37 21    ousmane.GUINDO@epicentre.msf.org   
Principal Investigator: Ousmane Guindo, MD         
Sponsors and Collaborators
Epicentre
Centre de Recherche Médicale et Sanitaire (Cermes), Niamey
Investigators
Principal Investigator: Francesco Grandesso, MSc Epicentre
Study Chair: Lynda Woi Messe, MD Epicentre
Study Chair: Ibrahim M Laminou, PhD Cermes
Study Chair: Jean-François Etard, PhD Epicentre
  More Information

No publications provided

Responsible Party: Epicentre
ClinicalTrials.gov Identifier: NCT01755559     History of Changes
Other Study ID Numbers: Epicentre/Nig/2012/Palu3ACT
Study First Received: December 19, 2012
Last Updated: February 4, 2014
Health Authority: Niger: Institutional Review Board

Keywords provided by Epicentre:
malaria
artemisinin
artemisinin-based combination therapies
Plasmodium falciparum
efficacy

Additional relevant MeSH terms:
Malaria
Malaria, Falciparum
Protozoan Infections
Parasitic Diseases
Amodiaquine
Artemether
Artemisinins
Artesunate
Dihydroquinghaosu
Piperaquine
Lumefantrine
Artemether-lumefantrine combination
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antifungal Agents
Coccidiostats
Schistosomicides
Antiplatyhelmintic Agents
Anthelmintics
Amebicides

ClinicalTrials.gov processed this record on April 16, 2014